Obesity Reviews - 2018 - Wilding - Obesity in The Global Haemophilia Population Prevalence Implications and Expert

obesity reviews doi: 10.1111/obr.
12746
Obesity Prevalence
Obesity in the global haemophilia population:

prevalence, implications and expert opinions
for weight management
J. Wilding1 , N. Zourikian2, M. Di Minno3, K. Khair4, N. Marquardt5, G. Benson6, M. Ozelo7 and

C. Hermans8
1
Obesity and Endocrinology Research Group, Summary
Institute of Ageing and Chronic Disease, Overweight and obesity may carry a significant disease burden for patients with
Clinical Sciences Centre, University Hospital haemophilia (PWH), who experience reduced mobility due to joint inflammation,
Aintree, Liverpool, UK; 2 Pediatric/Adult muscle dysfunction and haemophilic arthropathy. This review aimed to define the
Comprehensive Hemostasis Center, CHU prevalence and clinical impact of overweight/obesity in the global population of
Sainte-Justine/Sainte-Justine University PWH. A detailed literature search pertaining to overweight/obesity in haemophilia
Hospital Center, Montréal, Québec, Canada; in the last 15 years (2003–2018) was conducted, followed by a meta-analysis of ep-
3
Department of Translational Medical idemiological data. The estimated pooled prevalence of overweight/obesity in
Sciences, Federico II University, Naples, Italy; European and North American PWH was 31%. Excess weight in PWH is associ-
4
Haemophilia Comprehensive Care Centre, ated with a decreased range in motion of joints, accelerated loss of joint mobility
Great Ormond Street Hospital for Children, and increase in chronic pain. Additionally, the cumulative disease burden of obesity
London, UK; 5 Institut für Experimentelle and haemophilia may impact the requirement for joint surgery, occurrence of peri-
Hämatologie und Transfusionsmedizin, operative complications and the prevalence of anxiety and depression that associ-
Universitätsklinikum Bonn, Bonn, Germany; ates with chronic illness. Best practice guidelines for obesity prevention and
6
Northern Ireland Haemophilia Comprehensive weight management, based on multidisciplinary expert perspectives, are considered
Care Centre and Thrombosis Unit, Belfast City for adult and paediatric PWH. Recommendations in the haemophilia context em-
Hospital, Belfast, UK; 7 International phasize the importance of patient education and tailoring engagement in physical
Haemophilia Training Centre (IHTC) ‘Claudio activity to avoid the risk of traumatic bleeding.
L.P. Correa’, INCT do Sangue Hemocentro
UNICAMP, University of Campinas, Campinas, Keywords: Haemophilia, obesity, prevalence, weight management.
Brazil; and 8 Division of Haematology,
Haemostasis and Thrombosis Unit, Abbreviations: BMD, bone mineral density; BMI, body mass index; CDC, Centers
Haemophilia Clinic, Cliniques Universitaires for Disease Control and Prevention; CI, confidence interval; CVD, cardiovascular
Saint-Luc, Brussels, Belgium disease; FIX, factor IX; FVIII, factor VIII; HIV, human immunodeficiency virus;
MSK, musculoskeletal; PK, pharmacokinetics; PWH, patients with haemophilia;
Received 10 May 2018; accepted 24 June US, United States; WHO, World Health Organization.
2018
Address for correspondence: J Wilding DM

FRCP, Obesity and Endocrinology Research
Group, Institute of Ageing and Chronic
Disease, Clinical Sciences Centre, University
Hospital Aintree, Liverpool L9 7AL, UK.
E-mail: j.p.h.wilding@liverpool.ac.uk
© 2018 The Authors. Obesity Reviews published by John Wiley & Sons Ltd Obesity Reviews 19, 1569–1584, November 2018
on behalf of World Obesity Federation
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1570 Obesity in the global haemophilia population J. Wilding et al. obesity reviews
Introduction In the context of haemophilia, overweight and obesity are

expected to further add to the burden of disease; however,
Haemophilia is an X-linked, hereditary disorder of their prevalence in the global haemophilia population is cur-
haemostasis caused by the deficiency or complete absence rently unclear. This review was carried out with three main
of clotting factor VIII (FVIII, haemophilia A) or factor IX objectives: (i) to review available data on the global preva-
(FIX, haemophilia B) (1). The condition is estimated to af- lence of overweight/obesity in haemophilia, and whether
fect 400,000 people globally and is characterized by easy this differs to the general population; (ii) to define the im-
bruising, excessive bleeding and haemorrhage into the joints pact of overweight/obesity, as the disease may carry worse
(2). Spontaneous joint bleeds comprise up to 80% of all implications for the haemophilia population; and (iii) to
bleeding episodes in patients with haemophilia (PWH), with outline weight management guidelines that are relevant for
recurrent bleeding into ‘target joints’ progressively leading promoting safe and effective weight loss, suggesting best
to pain, restriction of movement and potentially irreversible practice for weight management in PWH, based on multi-
structural damage that form the hallmark of haemophilic disciplinary expert perspectives.
arthropathy (2,3).
Patients are treated with intravenous replacement of coag-
Methodology
ulation FVIII and FIX as standard of care. Replacement fac-
tor is dosed according to body weight and aims to arrest or
Literature search
prevent excessive bleeding when administered on-demand
or as prophylaxis (2). Historically, patients were not treated To identify all relevant studies for potential inclusion in this
routinely with replacement factor amid fear of viral contam- review, a detailed search pertaining to overweight/obesity
ination or due to lack of access to treatment in developing na- and haemophilia was conducted. A systematic search of
tions, leading to an older haemophilia population with manuscripts published within the last 15 years (01 January
damaged joints, decreased mobility and chronic synovitis 2003–18 January 2018) was performed in the electronic da-
(4,5). As access to virus-free coagulation factor has in- tabase PubMed (https://www.ncbi.nlm.nih.gov/pubmed),
creased, younger PWH in developed countries are often using the following search terms in all possible combina-
treated with routine intensive prophylaxis regimens and ben- tions: obese, obesity, overweight, weight, weight manage-
efit from a reduced physical impact of haemophilia and pres- ment, body weight, adiposity, haemophilia, hemophilia.
ervation of musculoskeletal function (2,5). However, the Non-English language and non-human articles were
availability of replacement factor for prophylactic treatment excluded from the results.
still varies between regions, with continued restricted access The literature search identified 476 articles, of which 90
in developing nations and poor long-term outcomes ob- were deemed potentially relevant for inclusion following
served with episodic treatment (2,5). Emerging therapies, manual review. Results have been reported as a flow
such as non-factor replacement therapy and gene therapy, diagram (Fig. 1).
have the potential to correct haemostasis and improve treat-
ment outcomes for PWH (6). Advances in treatment may al-
Meta-analysis
low greater scope to address comorbidities that impact
haemophilia management, including overweight and obe- To investigate the prevalence of overweight and/or obesity
sity. Despite any prospective improvements in treatment, in the global population of PWH, a meta-analytical evalua-
the risk of excessive bleeding is likely to remain a serious tion of prevalence data in epidemiological studies was per-
problem for the foreseeable future. formed. Studies included in the analysis were selected from
‘Overweight’ and ‘obesity’ are often classified according the 90 records identified in the original literature search.
to the following body mass index (BMI) categories in adults: Of these 90 records, the 28 studies that reported the number
healthy weight (BMI 18.5–24.9 kg m 2), overweight (BMI of enrolled PWH with overweight and/or obesity, or the per-
25–29.9 kg m 2), obese (BMI ≥30 kg m 2) or severely obese centage prevalence, were included in the meta-analysis
(BMI ≥40 kg m 2) (7,8). The World Health Organization (Table 1).
estimates that obesity prevalence in the general population For each study included, data regarding sample size, age
has tripled since 1975 and now affects approximately of the study population and country of origin of enrolled
13% of adults globally; a further 39% of adults are classi- patients were extracted. The primary analysis was the as-
fied as overweight (7). The obesity epidemic carries signifi- sessment of the pooled prevalence of overweight and/or
cant health implications for the general population, obesity in the global population of PWH. Due to a lack of
including increased risk of high blood pressure, type 2 world data, an additional analysis was performed for
diabetes, stroke, coronary heart disease, osteoathritis, sleep pooled prevalence in European and North American
apnea, kidney disease, liver disease, clinical depression and PWH. For the sensitivity analyses, results were stratified
certain types of cancer (7–12). according to age group (adult versus paediatric PWH) and
Obesity Reviews 19, 1569–1584, November 2018 © 2018 The Authors. Obesity Reviews published by John Wiley & Sons Ltd
obesity reviews Obesity in the global haemophilia population J. Wilding et al. 1571
Figure 1 Study selection flow diagram. *Several of the records identified are relevant for multiple subcategories. CVD, cardiovascular disease; MSK,
musculoskeletal; PK, pharmacokinetics.
region (North American versus European PWH). Statistical and UK identified total rates of overweight/obesity as 58%
analysis was carried out using Comprehensive Meta- in the haemophilia context versus 61% in the general age-
analysis Software (Version 2, Biostat, Englewood NJ, matched population (31). The overall rates of overweight/
2005). The prevalence of overweight and/or obesity was obesity reported in a 2001 paediatric Dutch population of
expressed as weighted mean prevalence with pertinent PWH and a non-haemophilia control group were 15%
95% confidence intervals (CI). The overall effect was tested and 17%, respectively (33). More recently in 2011, a sepa-
using z-scores, with significance set at p < 0.05. rate Dutch population of adult PWH recorded higher rates
of obesity in 100 PWH (19%) versus 200 non-haemophilic,
age-matched controls (13%) (28).
How prevalent is obesity in patients with
However, some studies of global populations of PWH re-
haemophilia?
port a reduced prevalence of overweight/obesity when com-
There is a growing population of PWH surviving to ad- pared with the general population. An obesity prevalence
vanced ages due to improved management of haemophilia rate of 19.6% was observed in a US population of 56 adult
from routine access to replacement coagulation factors (4). PWH (2006–2009), which was lower than the 31.9% ob-
Consequently, the ageing population of PWH are at risk served in the comparison population of non-haemophilic in-
of age-related diseases, including obesity and associated dividuals (15). In Germany, 10% of 29 elderly (≥60 years)
conditions, such as type 2 diabetes (4,41). Epidemiological PWH were affected by obesity versus 21% in an age-
studies were assessed to determine the prevalence of PWH matched control population (2006–2008) (36). In Taiwan,
across different age groups and regions. obesity was observed in 9% of PWH in a population-based
The majority of available epidemiological data for PWH analysis of 1,054 PWH versus 30% in 10,540 members of
and non-haemophilic controls suggest that the prevalence the general, age-matched population (1997–2010) (40).
of overweight/obesity in haemophilia is comparable with Additionally, a lower mean BMI (19.1 kg m 2) was re-
that observed in the general population. In the USA, in a ported in 50 Indian PWH compared with age-matched,
2011 study, 34.6% of 185 PWH had obesity compared with non-haemophilic controls (23.6 kg m 2) (43). In Mexico,
36.2% in a national survey of the general population (23). the cumulative rate of overweight/obesity was lower in 62
Similarly, 58.0% of adult PWH in the 2005 US Universal paediatric PWH (34%) versus the same number of age-
Data Collection Program had overweight/obesity versus matched controls (42%) (39).
54.9% in the general population (42). In Europe, a cross- To provide a more definitive estimate of global
sectional assessment of 709 PWH from the Netherlands overweight/obesity prevalence in PWH, a meta-analytical
Table 1 Epidemiology data included in the meta-analysis for overweight/obesity in adult and paediatric populations of PWH from different regions
Authors Year Region Age group Year of N, PWH and Prevalence in PWH and [non-haemophilic controls]* (%)
analysis [non-haemophilic
Overweight Obesity Overweight
controls]* 2 2
(BMI 25–29.9 kg m ) (BMI ≥30 kg m ) and obesity
2
(BMI ≥25 kg m )
North America
CDC (13) 2011 US Adult 2011 10,094 33.1 – –
US Paediatric 2011 8,164 20.8 – –
Curtis R et al. (14) 2015 US Adult 2005–2013 141 23 24 47
Lim MY et al. (15) 2011 US Adult 2006–2009 56 – 19.6 [31.9] –
Majumdar S et al. (16) 2010 US Adult 2008–2010 59 36 32 68
US Paediatric 2008–2010 73 21 16 37
Obesity Reviews 19, 1569–1584, November 2018

McNamara M et al. (17) 2014 US Adult 2010–2011 88 48.9 18.2 67.0
Minuk L et al. (18) 2015 Canada Adult 2000–2011 294 – 23.5 –
Monahan PE et al. (19) 2011 US Paediatric 1998–2008 6,420 16.1 20.7 36.8
1572 Obesity in the global haemophilia population
Revel-Wilk S et al. (20) 2011 Canada Paediatric 1999–2005 170 14.1 14.7 28.8
Ross C et al. (21) 2009 US Paediatric 2005–2007 37 16 3 19
Seaman CD et al. (22) 2016 US Adult 2009–2011 3,607 [8,025,025] – 5.2 –
[9.0]
Sharathkumar AA et al. (23) 2011 US Adult 2004–2008 185 – 34.6 –
[36.2]
Sood SL et al. (24) 2015 US Adult 2010–2012 165 – 30.3 –
J. Wilding et al.
Soucie JM et al. (25) 2011 US Paediatric 1998–2008 6,347 15.1 17.4 32.5
Ullman M et al. (26) 2014 US Adult 1998–2008 10,814* 35 28 63
US Adolescent 1998–2008 16 22 38
US Paediatric 1998–2008 16 20 36
Wiktop M et al. (27) 2017 US Adult 2013–2014 381 36.2 28.6 64.8
Europe
Biere-Rafi S et al. (28) 2011 The Netherlands Adult – 100 [200] – 19 –
[13]
Douma-van Riet DC et al. (29) 2009 The Netherlands Paediatric 2007 158 11.4 4.4 15.8
Fransen van de Putte DE et al. (30) 2012 The Netherlands Adult 1985–2010 408 – 8.5 49
[11.2] [52]
Fransen van de Putte DE et al. (31) 2013 The Netherlands Adult 2009–2011 388 44 9 53
[37] [12] [49]
UK Adult 2009–2011 321 42 22 64
[41] [20] [61]
Henrard S et al. (32) 2011 Belgium Adult 2003–2010 46 30.4 13.0 43.5
Hofstede FG et al. (33) 2008 The Netherlands Adult 2001 734 35 8 42
[50] [8] [58]
The Netherlands Paediatric 2001 332 10 6 15
[14] [3] [17]
(Continues)
© 2018 The Authors. Obesity Reviews published by John Wiley & Sons Ltd
obesity reviews

(BMI ≥25 kg m )
*Additional data included for non-haemophilic control populations were available. BMI, body mass index; CDC, Centers for Disease Control and Prevention; N, number of patients assessed for overweight/obesity;
2
evaluation of epidemiological data was performed across
and obesity
Overweight
Prevalence in PWH and [non-haemophilic controls]* (%) studies from different regions (Table 1). The overall pooled
prevalence of overweight/obesity from available data in the
global haemophilia population was 17% (95% CI: 15.0–
54.4
28.8
42.5
[74]
[50]
[42]
62
64
34
–
19.3); this estimation rose to 31% (95% CI: 26.8–36.2%)
when assessing European and North American populations
(BMI ≥30 kg m )
2
alone. Stratification by patient age showed an increased

Obesity
prevalence in adult (43.3%) versus paediatric (26.9%)

patients (Fig. 2). The overall pooled prevalence of
overweight/obesity by region was higher in European adults
13.0
13.8
[21]
[26]
[30]
10
26
17
9
–
(49.1%) versus North American adults (38.5%), but lower
in European paediatric patients (18.8%) when compared
(BMI 25–29.9 kg m )
2
with their North American counterparts (30.6%). A pro-

gressive increase in obesity prevalence over time was seen
Overweight
both in adult and paediatric populations (Fig. 3), reflecting

trends observed in the global obesity population (7). How-
ever, an ~20% increase in overweight/obesity was reported
41.4
[53]
[16]
15
52
38
17
in adults during a 10-year period, whereas an ~40%

–
increase was observed in children (Fig. 3).

Results from the meta-analysis demonstrate significant
[non-haemophilic
N, PWH and
1,054 [10,540]
levels of overweight/obesity in haemophilia communities

controls]*
from Europe and North America, especially with regard to

40 [40]
62 [62]
adult patients, which may in part be influenced by an ageing

531
84
29
50
2011–2013
2006–2008
1997–2010
analysis
Year of
2012
2008
2016
Adult/Paediatric
Age group
Paediatric
Paediatric
Adult
Adult
Adult
Adult
(cross-sectional)
Region
Figure 2 Pooled prevalence of overweight/obesity in adult and paediat-

Germany
ric populations of North American and European PWH. PWH, patients with
Mexico
Europe
Taiwan
haemophilia.
Italy
UK
UK
2016
2012
2009
2008
2016
2007
2015
Year
PWH, patients with haemophilia.

von Mackensen S et al. (38)
Tlacuilo-Parra A et al. (39)

Miesbach W et al. (36)
Sartori MT et al. (37)

Holme PA et al. (34)
Wang JD et al. (40)

(Continued)
Khair K et al. (35)
Figure 3 Changes in prevalence of overweight/obesity in global adult

Table 1
Authors
Global
and paediatric populations of PWH over time. PWH, patients with

haemophilia.
population of PWH. The estimated rate of 31% PWH who are affected by underweight, overweight and
overweight/obesity in European and US PWH, as well as obesity with greater efficiency (41). Additionally, some evi-
the rapid increase in overweight/obesity prevalence in paedi- dence suggest that dosing according to ‘ideal body weight’
atric PWH over a relatively short period is cause for signif- for height may allow for a significant reduction in factor
icant concern (16,17,26,27,31,36,38). Overweight/obesity consumption in people with overweight/obesity, which can
data for PWH are available from a limited number of coun- reduce the healthcare cost of prophylaxis while maintaining
tries; more epidemiological data from outside Europe and patient safety (52,53).
North America are needed to further elucidate the preva- Overweight/obesity also has implications on the adminis-
lence of overweight/obesity in the global haemophilia popu- tration of coagulation factor. PWH who have overweight/
lation. Additionally, as the majority of epidemiological obesity were less likely to use home-infusion or self-infusion
studies in PWH fail to account for percentage body mass of factor concentrate prophylactically in a population of
or lean body mass, the occurrence of clinically significant 10,814 male PWH A and B versus normal-weight individ-
excess weight in PWH may be underestimated (44). Further uals, possibly due to increased difficulty with venous access
studies that directly compare overweight/obesity between (26). Therefore, this cohort may be unable to take full ad-
PWH and age-matched, non-haemophilic controls will help vantage of benefits associated with home treatment, includ-
to define the prevalence of obesity in haemophilia. ing an improvement in quality of life and a reduction in
pain, disability and time spent in hospital (26).
What is the clinical impact of obesity in patients

with haemophilia? Musculoskeletal health
Spontaneous joint bleeds comprise up to 80% of bleeding
Dosing and administration of factor replacement
phenotype in PWH (2). For patients with severe disease,
Intravenous replacement coagulation factor products are intra-articular changes resulting from recurrent bleeding
the standard of care for the management of haemophilia into the joints lead to restricted movement, structural dam-
and are dosed according to body weight (2). Pharmacoki- age and the development of haemophilic arthropathy (3).
netic outcomes of factor dosing are influenced by Muscle haematomas can further contribute towards long-
overweight/obesity due to reduced plasma volume in adi- term damage, causing inflammation, infections, muscle dys-
pose tissue (45). Investigation into the pharmacokinetic im- function or a decreased range of motion (54,55). For the
plications of overweight/obesity in PWH suggests that population of PWH in the USA who are affected by
increased body weight has no significant impact on FVIII overweight/obesity, excess adiposity has been associated
activity, half-life, mean residence time and endogenous with a decreased range in motion in weight-bearing joints
thrombin potential of coagulation products (46,47). How- and accelerated loss of joint mobility (25,56,57). In
ever, in vivo recovery of FVIII is significantly dependent Europe, this reduction was reflected in paediatric PWH with
on BMI in PWH (48); infusing a similar amount of clotting overweight/obesity, who experienced a significant decrease
FVIII would result in a higher circulating FVIII level in in active range in flexion of the knees and elbows (29). Fur-
plasma of a person with obesity versus without, suggesting thermore, it has been reported that overweight/obesity in-
that this cohort is likely being ‘over’-treated (47–50). Con- creased the number of joint bleeds and reduced function of
versely, PWH who have a reduced BMI (<20 kg m 2) the lower limbs in a Dutch haemophilia cohort, while others
may experience lower FVIII recovery; if underdosed, these have identified an association between obesity and the oc-
patients would be at greater risk of spontaneous bleeds currence of chronic pain (27,58).
and subsequent joint damage (49). Evidence suggests that severe haemophilia may poten-
For PWH B, FIX has a higher clearance, longer half-life tially induce sarcopenia and decrease maximal muscle
and a larger volume of distribution compared with FVIII strength, possibly due to reduced engagement in physical ac-
(51). Consumption of FIX will increase in people with tivity to prevent bleeds and preserve joint health (59–62).
overweight/obesity due to dosing by body weight (51); how- Furthermore, the reduced mobility and loss of muscle func-
ever, further investigation is needed to explore the impact of tion observed with severe haemophilic arthropathy leads to
excess adiposity on in vivo recovery and FIX inactivity and subsequent muscle atrophy, which may in
pharmacokinetics. turn increase the risk of weight gain (2). In the general pop-
Individual variations in response to treatment mean that ulation, overweight/obesity is significantly associated with
standard weight-based prophylaxis regimens may fail to ad- reductions in whole muscle and fascicle strength (63), with
equately prevent bleeding in some patients or be a negative impact on skeletal muscle maintenance and re-
overused/excessively administered in others. Personalized generation, and reduction in muscle functionality and dete-
prophylaxis, with flexibility in dose and frequency of ad- rioration in muscle mass (64–67). Although there is
ministration, may therefore offer the opportunity to dose currently no evidence in the context of PWH affected by
overweight/obesity, it can be postulated that comorbidity in PWH who are affected by overweight/obesity, highlight-
with excess weight and haemophilia may place patients at ing the importance of effective weight management to reduce
a greater risk of reduced muscle strength and function. the requirement for surgical intervention.
In addition to joint health and muscle strength, several
European, US and global studies have identified osteopenia
Cardiovascular impact
and osteoporosis as severe comorbidities of haemophilia
(59,68–70). In the general population, high BMI is reported Overweight and obesity are well-established risk factors for
to have a positive correlation with bone mineral density cardiovascular disease (CVD), diabetes risk, hypertension,
(BMD), suggesting a protective effect of overweight/obesity type 2 diabetes and metabolic syndrome (79–82). For
against the occurrence of osteoporosis; however, discrep- haemophilia, there is discrepancy in the literature regarding
ancy in the literature regarding the impact of excess adipos- its impact on CVD. A recent 2017 review noted a lack of
ity on fracture risk means that the relationship between consensus for haemophilia’s effect on CVD risk factors, in-
obesity and bone health remains unclear (71,72). Similarly, cluding diabetes and atherosclerosis (83). Despite those au-
for PWH, the true impact of BMI on BMD has not been thors determining an increased prevalence of hypertension
established. One study reported a 58% prevalence of in PWH (83), more recent literature has demonstrated con-
osteoporosis/osteopenia in an Iranian population of PWH flicting results. A cross-sectional study of European PWH
and noted that patients with osteoporosis had a significantly reported a 45% prevalence of hypertension, which was
higher mean BMI than patients with osteopenia or a normal comparable with the non-severe haemophilia and non-
BMD (73). By contrast, assessment of 30 US PWH found a haemophilic population (34). Meanwhile, a 2017 study
significant association with osteoporosis and lower BMI found a significantly decreased prevalence of hypertension
(74). Furthermore, a meta-analysis including European, in a cross-sectional analysis of US haemophilic (39.5%) ver-
Asian, South American, North African and Australian sus non-haemophilic (56.3%) individuals (22).
PWH assessing the lumbar spine found no evidence that There are also contradictory reports over the impact of
BMI could be used to predict BMD (75). Despite this incon- haemophilia on the occurrence of CVD events. One review
sistency within the literature, the association of low BMD identified studies reporting reduced risk, comparable risk
with increased haemophilic arthropathy, reduced mobility or elevated risk of CVD events, such as ischaemic stroke
and muscle atrophy (2) stresses the importance of address- and peripheral arterial disease, in PWH compared with the
ing bone health and identifying the impact that general population (84). In the context of overweight/
overweight/obesity has on BMD in the context of obesity, excess adiposity was not a risk factor for CVD
haemophilia. events in a population of US PWH (23). Similarly, another
report found no association between obesity and the inci-
dence of atherothrombotic events in Taiwanese patients
Invasive procedures
(40). However, BMI was significantly associated with in-
The availability of replacement factor concentrates has creased risk for hypertension in European PWH (34). This
allowed major surgical procedures to be performed safely continued discrepancy in the literature highlights the need
in PWH, who often require joint replacement surgery fol- for investigational studies to determine the impact of
lowing recurrent bleeding into target joints and subsequent haemophilia on CVD prevalence and risk factors, explore
chronic arthropathy (76). In the general population, obesity the effect of other predictors of CVD incidence, and investi-
can accelerate the development of osteoarthritis due to in- gate the implications of increased BMI in PWH. However,
creased mechanical load or metabolic disruption, placing the large epidemiological studies required to identify BMI
patients at greater relative risk for total knee or hip as an independent risk factor for CVD in the general
arthroplasty (77). Additionally, it has been reported in the population (85,86) may pose a considerable challenge to re-
USA that people with obesity undergoing total joint produce in the comparatively limited global population of
arthroplasty are subject to greater risk of perioperative com- PWH.
plications (78).
In the context of haemophilia, total knee replacement
Psychological impact
carries an increased reported infection prevalence (0–17%)
versus the non-haemophilic population (1–2%) (76). Fur- Chronic illnesses carry a significantly increased risk of clin-
thermore, obesity is associated with a more rapid impair- ical depression compared with the general population,
ment of joint function in PWH versus patients without which may be caused by anxiety about health outcomes
obesity, implying a greater requirement for surgery (25,57). and disease management, or by the biological impact of
Although further evidence in the context of haemophilia is the disease (87,88). Despite a lack of clinical data on excess
needed, these findings suggest that the risk for joint surgery weight in the context of haemophilia, the psychological im-
and perioperative complications may be further increased pact of overweight/obesity in PWH is likely to be
significant. In the general population, overweight/obesity is arthropathy, muscular atrophy and impaired mobility,
associated with stigmatization and discrimination that can which are in turn risk factors for obesity (4).
lead to the development of low self-esteem, depression, The management of haemophilia is a major burden for pa-
dysfunctional eating behaviours, mood disorders, compro- tients, especially with regard to frequent injections for pro-
mised perceived quality of life, anxiety and impaired body phylaxis and the resolution of bleeding events (94).
image (10,89). Treatment of overweight/obesity in PWH should be highly
Within the haemophilia community, the prevalence of de- integrated into the haemophilia treatment pathway to reduce
pression and psychological implications of the condition are the psychological impact of disease burden. Additionally,
also significant. The prevalence of depression was 32% in a dosing of replacement coagulation factor according to body
cohort of 307 PWH A in the UK, who were experiencing weight highlights the importance of monitoring and manag-
anxiety over managing stigma associated with having a ing weight in all PWH, regardless of BMI. Specific guidelines
bleeding disorder or contracting human immunodeficiency for weight management in the context of haemophilia do not
virus or hepatitis C through contaminated blood products currently exist; however, established guidelines for identify-
(90). Similarly, 37% of patients suffered from depression ing, preventing and treating overweight/obesity can be
in an analysis of 41 US PWH, with over two-thirds adapted to the haemophilia population.
reporting that symptoms relating to their depression caused
functional impairment of daily activities (91). The incidence
Screening tools for the identification of
of depression in this population was consistent with adults
overweight/obesity in haemophilia
suffering from other chronic illnesses, and significantly
higher than rates of depression observed in the general pop- Measurement of BMI is one of the most commonly used and
ulation of US males (4%) (91). High prevalence was also widely recommended methods for diagnosing the incidence
observed in Iranian PWH, where anxiety, depression and of overweight/obesity (95,96). In an evaluation of 90 US
psychiatric features were present in >60% of patients and haemophilia treatment centres, 67% of centres reported
were associated with chronic stress caused by fear of bleed- measuring BMI at clinic visits (97). However, BMI does
ing (92). Additionally, almost half (43%) of young adult not accurately predict body fat, as it does not discriminate
PWH participating in the global Haemophilia Experiences, between body fat percentage and lean mass (95,96). For ex-
Results and Opportunities initiative reported the occurrence ample, patients with a high muscle mass may classify as hav-
of stress, depression, insomnia and anxiety; 26% of patients ing ‘overweight’ or ‘obesity’ according to their BMI, even in
attributed this directly to having haemophilia (93). Despite the absence of excess fat. Therefore, alternative screening
recommendations for psychological support in haemophilia tools may be required to provide a definitive diagnosis of
guidelines, these patients indicated a lack of involvement overweight/obesity (8). The measurement of waist circum-
from counsellors and social workers as part of their ference has been identified as a strong predictor of visceral
haemophilia treatment (93). Along with the significant obesity and a more accurate measure than BMI for
incidence of depression in patients with chronic illnesses, determining obesity health risks (95). Alternatively, waist-
including both overweight/obesity and haemophilia, these to-height ratio has been reported as the most accurate
outcomes highlight the need for psychological support as predictor of whole body fat percentage and visceral adipose
an important aspect of disease management in PWH af- tissue when compared with BMI, waist circumference and
fected by overweight/obesity. waist-to-hip ratio (98). These alternative screening tools
should be considered as an additional assessment in con-
junction with BMI in order to more accurately record body
How can prevention and treatment of
weight composition. Additionally, plotting BMI and height–
overweight/obesity be addressed in patients
weight percentile charts may help to assess the development
with haemophilia? Expert opinion on weight
of overweight/obesity over time and subsequent need for
management strategies
weight management intervention in PWH (95,99).
Although haemophilia itself is unlikely to be a causal factor
for obesity, the disease may indirectly lead to weight gain or
Prevention of overweight/obesity
difficulty in weight loss if patients reduce levels of exercise
due to muscle/joint pain, restricted range of movement or Patients with haemophilia of a healthy weight (BMI
fear of bleeding. According to a 2006 US survey, as many 18.5–24.9 kg m 2) should be encouraged to maintain
as 60% of paediatric and adolescent PWH avoid physical healthy lifestyle habits that prevent the occurrence of
activity to help manage their haemophilia (62). The risk of overweight/obesity (100,101); however, 89% of 90
weight gain may be especially relevant for the older popula- haemophilia treatment centres assessed in the USA had no
tion of PWH who were not treated routinely with prophy- protocol in place to address healthy weight in PWH (97).
laxis during their childhood and suffer from advanced Early intervention is especially important in the paediatric
Table 2 Lifestyle interventions for preventing overweight and obesity in PWH
Intervention Recommendations for the general population (100,101,103) Considerations in haemophilia
Energy • Estimated average requirements for energy per day: • Energy intake guidelines for preventing obesity should be similar
intake ○ Adult men: 10.9 MJ per day (2,605 kcals per day) between the general population and PWH
○ Adult women: 8.7 MJ per day (2,079 kcals per day) • For PWH affected by overweight/obesity who are less able to engage
in sport/exercise due to physical limitations or disability, energy
intake may need to be reduced accordingly
Physical • Engage in at least 150 min of moderate-intensity activity • Recommendations for the intensity, type and duration of physical
activity ○ i.e. 30 min exercise on at least 5 days a week activity will differ between the general population and PWH, as
• OR 75 min of vigorous-intensity aerobic activity physical activity is accompanied by a risk of traumatic bleeding in
• Avoid extreme physical activity (e.g. obsessive exercising, high- PWH (104)
intensity exercise that is difficult to sustain) that may not provide • Please see ‘Additional considerations for physical activity in patients
wider health improvements with haemophilia’
Dietary • Reduce the overall energy density of the diet • Dietary guidelines for preventing obesity should not differ between
habits • Increase consumption of fruits, beans, pulses and wholegrains the general population and PWH
• Limit consumption of energy dense food and drinks, particularly • When limiting consumption of certain foods, PWH should ensure that
‘fast’ or ‘takeaway’ foods adequate consumption of iron is maintained due to risk of iron
• Avoid food and drink with high sugar content deficiency with frequent bleeding (105)
• Reduce total fat intake • PWH should limit consumption of food/nutrients that may reduce
• Decrease size of food portions clotting ability (e.g. vitamin E and fish oil) (106,107)
• Include breakfast without increasing daily calorie intake • Additional considerations may be relevant for PWH who are infected
• Avoid snacking between meals with hepatitis C or HIV
HIV, human immunodeficiency virus; PWH, patients with haemophilia.
population to embed healthy lifestyle behaviours and mon- Regional considerations

itor weight status (102). Addressing weight management
It is important to acknowledge that the global management
may be easier in both adult and paediatric populations of
of overweight/obesity varies between different regions. The
PWH owing to frequent contact with the haematologist
World Health Organization definition for excess adiposity
(97). Recommendations for preventing excess weight gain
for Caucasian populations uses a BMI cut-off point of
and the occurrence of overweight/obesity in PWH are
≥25 kg m 2, which is supported by several European-
summarized in Table 2 alongside established guidelines for
specific and US-specific guidelines (7,103,108,117). How-
the general population.
ever, at a given BMI, South Asian, Southeast Asian and East
Asian communities have a higher percentage body fat than
Management of overweight and obesity their Caucasian counterparts and are at greater risk of
developing obesity-related comorbidities. Therefore, it is
Recommendations for management of overweight/obesity
recommended that a lower BMI cut-off point of ≥23 kg m 2
in adult and paediatric patients in PWH are summarized
be used to identify excess adiposity in these
in Tables 3 and 4, respectively, alongside established guide-
populations (117,118).
lines for the general population.
Additionally, perceptions of body weight may influence
motivation for people with overweight/obesity to partici-
Additional considerations for weight pate in weight loss programmes. For example, in some
management African communities, excess weight is traditionally associ-
ated with wealth, good health and higher socioeconomic
Goal setting status, while being thin associates with incidence of chronic
illness (119,120). An assessment of 78 focus group partici-
The management of overweight/obesity requires setting ap-
pants in South Africa found a low perception of threat to
propriate goals for weight loss and emphasizing realistic tar-
health from excess weight, and the belief that overweight
gets (108). Several European and US guidelines advise that a
is normal, rather than a disease (121). This poses a consid-
sustained weight loss of 5–10% body weight can lead to
erable challenge for healthcare providers to control excess
clinically meaningful benefits in the general population,
weight in these populations (121).
such as reducing CVD risk factors and diabetes risk
(103,108,114,115). However, despite 5–10% loss in body
weight often being stated as a realistic weight management
Management in children
target, the National Institute for Health and Care Excellence
in the UK notes that average weight loss following partici- Children are often screened for excess adiposity using age-
pation in a weight loss programme is ~3% (116). specific and sex-specific ‘BMI-for-age’ growth charts, which
Table 3 Guidelines for weight loss in adult PWH with overweight/obesity
Intervention General recommendations for adults (103,108) Considerations in haemophilia
Energy intake • Energy (calorie) intake should be reduced by 500–1,000 kcal • Energy intake guidelines for weight loss should not differ
per day or 15–30% between the general population and adult PWH
○ Restriction should be individualized and acknowledge
nutritional habits, physical activity, comorbidities and
previous dieting attempts
Physical activity • Engage in at least 150 min of moderate-intensity aerobic • As in Table 2
exercise, combined with 1–3 training sessions per week of
resistance exercise to increase muscle strength
• Increase non-exercise and active leisure activities (biking,
walking, gardening, golf) to reduce sedentary behaviour
Dietary habits • As above (prevention of overweight/obesity) • As in Table 2
• Providing an energy-restricted diet may require support from a
nutritionist or dietitian
• Food selection should be guided by available foods, which vary
from country to country
Behavioural • Includes interventions that enhance patient prescriptions to • Patient education is especially important in PWH. PWH affected
therapy reduce calorie intake and increase physical exercise by overweight/obesity should be made more aware that
• Interventions include self-monitoring of weight/food intake and ○ Haemophilia cannot be properly controlled without
physical activity, reasonable goal-setting, stimulus control, addressing BMI
controlling the process of eating and patient education ○ The time and energy invested in haemophilia treatment, and
the benefits from treatment, are at risk if patients do not
maintain a healthy weight
2
Pharmacotherapy • Can be considered for people with obesity (BMI ≥30 kg m ) or • Pharmacotherapy guidelines for weight loss should not differ
2
overweight with a BMI ≥27 kg m with an obesity-related between the general population and adult PWH
disease (e.g. hypertension and type 2 diabetes)
• Pharmacotherapy should be used only as an adjunct to lifestyle
therapy and not as stand-alone treatment
• Clinicians should consider differences in efficacy, adverse side
effects, cautions and warnings that characterize approved
medications, and consider the presence of weight-related
complications and medical history
• Some interventions may reduce absorption of fat soluble
vitamins (A, D, E and K) and may require supplementation
2
Bariatric surgery • Should be considered for patients with a BMI ≥40 kg m (or • Haemophilia may not be a contraindication to bariatric surgery
2
35.9–39.9 kg m with comorbidities) in the general population (109)
of people affected by obesity • However, the procedure requires careful consultation for PWH
• Requires lifelong medical monitoring and should only be due to increased bleeding risk. As with the general population,
considered if other weight loss attempts fail bariatric surgery may only be appropriate for a select group of
patients
• Some procedures (e.g. Roux-en-Y gastric bypass surgery) are
associated with malabsorption of iron and B12, folate
deficiency, and reduced absorption of fat soluble vitamins
(including vitamin K needed for synthesis of clotting factors)
can occur (110,111)
○ Hence, monitoring and replacement of micronutrients are a
particular concern for PWH due to bleeding risk
Psychological • Psychological support and/or treatment is an integral part of • Psychological support provided for obesity management
support obesity management and may require referral to a specialist should also address psychological implications regarding the
where there is evidence of eating disorders, anxiety, depression burden of haemophilia
or stress
BMI, body mass index; PWH, patients with haemophilia.
have defined overweight (85–<95th percentile) and obesity are still growing, they may only need to maintain body
(≥95th percentiles) categories (99). For patients with weight or slow their rate of weight gain (122).
overweight/obesity, the US Centers for Disease Control Weight management in children is influenced by the
and Prevention recommends that consultation from a weight, eating habits and lifestyle behaviours of family
healthcare professional should be provided before placing members. Children living with overweight parents/
paediatric patients on a weight loss programme; as children grandparents were found to be at greater risk of childhood
Table 4 Guidelines for weight loss in paediatric PWH with overweight/obesity
Intervention General recommendations for children/adolescents (112,113) Considerations in haemophilia
Energy intake • Reduce energy intake so that it falls below energy expenditure • Energy intake guidelines for weight loss should not differ
between the general population and paediatric/
adolescent PWH
Physical activity • Engage in 60 min of moderate or greater intensity physical activity • As in Table 2
each day
• Encourage increase in physical activity, even in the absence of weight loss
• Encourage a reduction in sedentary behaviour, such as playing video
games and watching television
Dietary habits • Minimize or eliminate sugar-sweetened drinks • As in Table 2
• Tailor dietary changes to food preferences and allow for a flexible and
individual approach to reducing calorie intake
• Dietary recommendations must be part of a multicomponent
intervention
Behavioural • Includes stimulus control, self-monitoring, goal-setting, rewards for • As in Table 3
therapy reaching goals, problem-solving
• Encouragement and reinforcement from parents/caregivers
Pharmacotherapy • Generally not recommended for children <12 years, except in • Pharmacotherapy considerations should not differ
exceptional circumstances (e.g. extreme comorbidity) between the general population and paediatric/
• Weight loss medication is approved for some adolescent patients and adolescent PWH
may be appropriate in select cases as an adjunctive therapy when
lifestyle intervention alone has been ineffective
Bariatric surgery • Generally not recommended in children or young people • Surgical considerations should not differ between the
○ There are exceptional circumstances for consideration for surgery, general population and paediatric/adolescent PWH
2
where the patient must be physically mature, have a BMI of ≥50 kg m
2
(or ≥40 kg m with significant comorbidities) and have failed other
formal weight loss programmes
BMI, body mass index; PWH, patients with haemophilia.
overweight and obesity (123). To address excess weight in with lipid accumulation in the liver and skeletal muscle, in-
children, National Institute for Health and Care Excellence ducing insulin resistance and greater risk of type 2 diabetes
recommends active involvement of the patient’s family (127). Additionally, diets rich in free sugar may increase the
members/carers, who can provide positive reinforcement chance of excess energy intake and indirectly promote the
of weight management prescriptions and help improve development of type 2 diabetes and CVD through weight
weight loss outcomes (124). Additionally, they report evi- gain (128). Although further evidence is required to verify
dence that targeting both parents and children, or whole the impact of high-sugar diets on body weight, the potential
families, is effective in reducing BMI scores by the end of a metabolic effects of excess sugar consumption highlight the
weight management programme, emphasizing the impor- importance of restricting sugar intake as part of weight loss
tance of family involvement (124,125). programmes.
Genetic effect Additional considerations for physical activity in

Genetic variation is an additional consideration with regard patients with haemophilia
to individualized weight management programmes. Hetero- Engagement in physical activity is an important component
geneous variations between patients may influence their sus- of weight management and in PWH can lower the risk of
ceptibility to different weight loss interventions. However, overweight/obesity (38,129). However, increased risk of
the use of genomic data to individualize weight manage- bleeding in PWH means that advice about physical exercise
ment programmes is currently speculative and requires should be individualized to the physical capabilities and
further research (126). preferences of the patient. Two reviews of physical activity
in haemophilia recommend that the development of an ex-
ercise regimen involves active input from the patient,
Sugar consumption
haemophilia treatment team, and a physiotherapist who is
Some evidence suggest that the excess consumption of fruc- knowledgeable on the pathophysiology of bleeding disor-
tose or monosaccharides in high-sugar diets is associated ders (130,131). Additionally, the exercise prescription
should include patient education around physical activity Table 5 Research questions for overweight/obesity in PWH
and regular assessment of musculoskeletal health (131). Research questions/topics in haemophilia

Prophylactic administration of replacement coagulation
1 What impact does overweight/obesity have on the implementation and
factors can help to reduce bleeding risk during exercise, efficacy of new treatment options in haemophilia, such as gene
and should be tailored to the individual needs of the patient therapy?
(130). 2 What impact does haemophilia have on body composition and how
A number of guidelines exist to assess the risk for trauma does it relate to future risk of diabetes and cardiovascular disease?
3 How efficacious and safe are pharmacotherapy interventions and
and bleeding prior to PWH participating in physical activ-
bariatric surgery in PWH affected by overweight/obesity?
ity. The World Federation of Hemophilia encourages partic- 4 How successful are lifestyle interventions in the context of PWH?
ipation in noncontact sports (e.g. badminton, cycling, golf 5 What impact does overweight/obesity have on bone mineral density in
and swimming) and suggests avoiding high contact and col- PWH?
lision sports (e.g. soccer and hockey) (2). However, for some 6 What is the psychological impact of overweight/obesity in the context
of PWH?
PWH, racquet sports may be associated with microbleeding,
7 Does overweight/obesity increase the risk for joint surgery in PWH?
chronic synovitis and early haemophilic arthropathy of the 8 What is the effect of overweight/obesity on the pharmacokinetics of FIX?
joints, which may not become apparent until more perma-
nent damage has been caused (N Zourikian, personal com- FIX, factor IX; PWH, patients with haemophilia.
munication) (132). Similarly, the National Hemophilia

Foundation ‘Playing it Safe’ recommends regular engage-
ment in noncontact sport and cites aquatics, hiking and Conclusion
Frisbee® as examples of low-risk activities (133). One study The global trend of increasing rates of overweight/obesity in
reported that activities least associated with risk of injury in- the general population is a cause for significant concern.
clude water polo, walking, cross-country skiing and swim- Epidemiological data suggest that the prevalence of
ming (134); however, water polo may still carry a high overweight/obesity in European and US PWH generally re-
risk of injury due to body contact that occurs underwater flects that observed in the non-haemophilic population;
(135). Despite recommendations for low-impact sports, a however, further assessment of PWH in developing nations
lack of difference in rates of injury and frequency of bleeds is needed to identify prevalence globally. The burden of
has been observed when comparing low-impact versus overweight/obesity may be particularly extensive in the
high-impact sports, suggesting that with proper supervision, haemophilia community, which is already at risk of blood-
PWH should be able to engage in a wide range of activities induced joint inflammation, muscle dysfunction and re-
(21,136). duced range of motion due to spontaneous bleeding and
haemophilic arthropathy. Overweight/obesity has
Benefits of physical activity implications for pharmacokinetics, musculoskeletal health,
CVD and psychological health, although further research
Physical activity offers PWH significant health benefits with is required to fully elucidate the impact of excess adiposity
regard to joint, muscle and psychological health. Regular in the context of haemophilia. Key research questions
physical activity has been seen to strengthen joint- requiring further investigation by the community of
supporting muscles and help slow or prevent haemophilic clinicians treating haemophilia and obesity have been
arthropathy by reducing the risk of damage, improving outlined in Table 5. The prevention and management of
joint flexibility and allowing better recovery from bleeds overweight/obesity in the context of PWH has additional
(104,130). In 50 adult PWH from the UK, there was a sig- considerations with regard to patient education, psycholog-
nificant improvement in overall health-related quality of life ical support and, perhaps most importantly, engagement in
and physical performance in patients participating in higher physical exercise. Weight management considerations need
levels of sport (38). An assessment of exercise in a popula- to be strongly integrated into the haemophilia treatment
tion of 30 Egyptian paediatric PWH demonstrated that pathway.
aerobic and resistance training increased BMD, muscle
strength and functional ability (137). The benefits of
physical activity are further supported by evidence in the
Conflict of interest statement
general population. Even in the absence of weight loss,
physical activity can increase lean body mass by initiating John Wilding has served as a consultant for Astellas,
skeletal muscle growth and have a positive effect on mental AstraZeneca, Boehringer Ingelheim, Janssen Pharmaceutica,
well-being, reducing levels of clinical depression (138). In Lilly, Napp Pharmaceuticals, Novo Nordisk and Sanofi.
addition, resistance training can promote lean mass and Nichan Zourikian has no competing interests. Matteo Di
improve overall muscle strength/endurance in patients with Minno has served as a board member for Bayer, Novo
limited mobility (139). Nordisk and Pfizer; a consultant for Bayer and Novo
Nordisk; a member of a speaker’s bureau for Pfizer; and has 5. Srivastava A. Haemophilia care – beyond the treatment
received grants from Novo Nordisk and Pfizer; and funding guidelines. Haemophilia. 2014; 20: 4–10.
6. Carr ME, Tortella BJ. Emerging and future therapies for
for educational presentations for Novo Nordisk. Kate Khair hemophilia. J Blood Med. 2015; 6: 245–255.
has received travel funding and served as a consultant for 7. World Health Organization (WHO). (2017). Obesity and over-
Novo Nordisk. Natascha Marquardt has received travel weight [WWW document]. http://www.who.int/mediacentre/
funding from Novo Nordisk; has served as a consultant for factsheets/fs311/en/
Bayer, CSL Behring, Novo Nordisk, Pfizer and Sobi; a mem- 8. National Health Service (NHS) UK. (2016). Obesity [WWW
document]. https://www.nhs.uk/conditions/obesity/
ber of a speaker’s bureau for Baxalta/Shire, Bayer,
9. Centers for Disease Control and Prevention. (2017). The health
Octapharma, Pfizer, Roche/Chugai and Sobi; has received effects of overweight and obesity [WWW document]. https://www.
an institutional research grant from Pfizer; received funding cdc.gov/healthyweight/effects/index.html
for educational presentations for Novo Nordisk; and 10. Djalalinia S, Qorbani M, Peykari N, Kelishadi R. Health
funding for additional activities from Baxalta/Shire, Novo impacts of obesity. Pak J Med Sci. 2015; 31: 239–242.
11. Arthritis Research Campaign. (2009). Osteoarthritis and obe-
Nordisk and Octapharma. Gary Benson has received travel
sity: a report by the Arthritis Research Campaign [WWW
funding from Novo Nordisk and served as a consultant and document]. https://www.arthritisresearchuk.org/external-resources/
a member of a speaker’s bureau for Novo Nordisk. 2012/09/17/15/29/osteoarthritis-and-obesity-a-report-by-the-arthritis-
Margareth Ozelo has received an institutional research grant research-campaign.aspx
from Bioverativ, Novo Nordisk, Pfizer and Shire; received 12. National Institute of Diabetes and Digestive and Kidney Dis-
eases (NIH). (2015). Health risks of being overweight [WWW
travel support from Novo Nordisk; has served as a consul-
document]. https://www.niddk.nih.gov/health-information/weight-
tant for Novo Nordisk; has served as a board member for management/health-risks-overweight
BioMarin, CSL Behring, Pfizer, Roche and Shire; and has 13. Centers for Disease Control and Prevention. (2011). Summary
served as a member of a speaker’s bureau for Pfizer, Roche report of UDC Activity National: risk factors by age (hemophilia)
and Shire. Cedric Hermans has received travel funding and [WWW document]. https://www2a.cdc.gov/ncbddd/htcweb/udc_
served as a consultant for Novo Nordisk. report/UDC_view1.asp?para1=NATION&para2=AGEH&para3=
&ScreenWidth=1680&ScreenHeight=1050
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obesity reviews doi: 10.1111/obr.

Obesity in the global haemophilia population:

J. Wilding1 , N. Zourikian2, M. Di Minno3, K. Khair4, N. Marquardt5, G. Benson6, M. Ozelo7 and

Address for correspondence: J Wilding DM

Introduction In the context of haemophilia, overweight and obesity are

Obesity Reviews 19, 1569–1584, November 2018

on behalf of World Obesity Federation

alone. Stratification by patient age showed an increased

prevalence in adult (43.3%) versus paediatric (26.9%)

with their North American counterparts (30.6%). A pro-

both in adult and paediatric populations (Fig. 3), reflecting

in adults during a 10-year period, whereas an ~40%

increase was observed in children (Fig. 3).

levels of overweight/obesity in haemophilia communities

from Europe and North America, especially with regard to

adult patients, which may in part be influenced by an ageing

Figure 2 Pooled prevalence of overweight/obesity in adult and paediat-

PWH, patients with haemophilia.

Tlacuilo-Parra A et al. (39)

Sartori MT et al. (37)

Wang JD et al. (40)

Khair K et al. (35)

Figure 3 Changes in prevalence of overweight/obesity in global adult

and paediatric populations of PWH over time. PWH, patients with

What is the clinical impact of obesity in patients

Table 2 Lifestyle interventions for preventing overweight and obesity in PWH

Intervention Recommendations for the general population (100,101,103) Considerations in haemophilia

HIV, human immunodeficiency virus; PWH, patients with haemophilia.

population to embed healthy lifestyle behaviours and mon- Regional considerations

Table 3 Guidelines for weight loss in adult PWH with overweight/obesity

Intervention General recommendations for adults (103,108) Considerations in haemophilia

BMI, body mass index; PWH, patients with haemophilia.

Table 4 Guidelines for weight loss in paediatric PWH with overweight/obesity

Intervention General recommendations for children/adolescents (112,113) Considerations in haemophilia

BMI, body mass index; PWH, patients with haemophilia.

Genetic effect Additional considerations for physical activity in

and regular assessment of musculoskeletal health (131). Research questions/topics in haemophilia

munication) (132). Similarly, the National Hemophilia

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